期刊
AGING CELL
卷 14, 期 1, 页码 49-59出版社
WILEY
DOI: 10.1111/acel.12293
关键词
apolipoprotein E; age; DNA methylation; variants; epidemiology; interaction
资金
- National Heart Lung and Blood Institute [U01HL072524-04, 5R01HL1043135-04]
- National Institute of Neurological Disorders and Stroke [T32NS054584]
- USDA [58-1950-0-014]
- [K08 HL112845]
Although apolipoprotein E (APOE) variants are associated with age-related diseases, the underlying mechanism is unknown and DNA methylation may be a potential one. With methylation data, measured by the Infinium Human Methylation 450 array, from 993 participants (age ranging from 18 to 87years) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study, and from Encyclopedia of DNA Elements (ENCODE) consortium, combined with published methylation datasets, we described the methylation pattern of 13 CpG sites within APOE locus, their correlations with gene expression across cell types, and their relationships with age, plasma lipids, and sequence variants. Based on methylation levels and the genetic regions, we categorized the 13 APOE CpG sites into three groups: Group 1 showed hypermethylation (>50%) and were located in the promoter region, Group 2 exhibited hypomethylation (<50%) and were located in the first two exons and introns, and Group 3 showed hypermethylation (>50%) and were located in the exon 4. APOE methylation was negatively correlated with gene expression (minimum r=-0.66, P=0.004). APOE methylation was significantly associated with age (minimum P=2.06E-08) and plasma total cholesterol (minimum P=3.53E-03). Finally, APOE methylation patterns differed across APOE epsilon variants (minimum P=3.51E-05) and the promoter variant rs405509 (minimum P=0.01), which further showed a significant interaction with age (P=0.03). These findings suggest that methylation may be a potential mechanistic explanation for APOE functions related to aging and call for further molecular mechanistic studies.
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